In junior and senior high school science you learn that proteins are chains of amino acids, and that nucleic acids (DNA and RNA) carry genetic information. At the end of the 19th century, almost nothing was known about their detailed chemical structures. Kossel developed new chemical separation techniques and isolated the bases that make up nucleic acids. He obtained pure crystals of adenine, cytosine, thymine, guanine, and uracil and determined their elemental composition. His work demonstrated that nucleic acids consist of sugar, phosphate, and bases, laying the foundation for understanding how living organisms store information. He also discovered histones, basic proteins that hinted that DNA is packaged with proteins to form chromosomes. Kossel’s studies gave birth to the disciplines of biochemistry and molecular biology and directly fueled advances in medicine and biotechnology. Modern genetic testing and vaccine development stand on the extension of the groundwork he provided.

Focusing on the nuclear substance “nuclein,” Kossel began systematic component analysis of cell nuclei in the 1880s. After sulfuric hydrolysis he quantified phosphate and then fractionated the products using barium and silver salts, enabling him to separate individual bases. By 1891 he had isolated the purine bases adenine and guanine and the pyrimidine bases cytosine, thymine, and uracil, determining their empirical formulas. He also inferred the presence of ribose and deoxyribose in nucleic acids, paving the way for the later distinction between DNA and RNA. Moreover, he discovered the basic protein family histones and proposed that their strong positive charge interacts electrostatically with the negatively charged DNA to form chromatin. These findings connected directly to Fischer’s peptide bond concept and to Levene’s nucleotide theory, ultimately supporting the Watson–Crick double helix model of the mid-20th century. Kossel’s quantitative analyses, employing state-of-the-art acid–base titration and elemental analysis, anticipated the principles of modern LC-MS and HPLC separation. His work introduced a “molecular medicine” viewpoint to medical science, highlighting that diseases could be traced to abnormalities in proteins or nucleic acids, and stimulated research into the diagnosis and treatment of genetic disorders. By the time the prize was awarded in 1910, his students were already engaged in stepwise amino-acid degradation and synthetic peptide chemistry, heralding rapid advances in protein science. Kossel’s achievements can therefore be regarded as the conceptual starting point of modern life sciences that aim to explain biological phenomena on a molecular scale.

Building on Schulze’s earlier work, Kossel refined the concentrated H2SO4/BaSO4 precipitation method to quantitatively isolate base fractions after nucleic-acid hydrolysis. He established the purine skeletons of adenine and guanine and the pyrimidine skeletons of cytosine, thymine, and uracil, deriving molecular formulas such as C5H4N4O and C4H5N3O from nitrogen content, a groundbreaking achievement. By showing that base molar ratios vary among tissues and species, he foreshadowed the later re-evaluation of Chargaff’s rules. His report that histones are enriched in basic amino acids (lysine, arginine) and remain acid-soluble yet tightly DNA-bound laid the foundation for chromatin structural theory. Kossel’s data underpinned Levene’s tetranucleotide hypothesis and were carried forward into Astbury’s X-ray diffraction analyses. Although he lacked direct sequence determination, he inferred the presence of phosphodiester bonds from titration curves of partial hydrolysates. Collaborating with Behringwerke (now Roche) in 1902, he developed synthetic routes for bases enabling industrial-scale production of pharmaceutical precursors, an important contribution to applied biochemistry. In his award lecture, he envisaged protein turnover in vivo and discussed the dynamic equilibrium of nucleic-acid–protein complexes, anticipating later epigenetic concepts. His traceable analytical protocols contributed to later ISO standards in chemical metrology and are still applied in food analysis and environmental monitoring. Evaluating his achievements, one should highlight how he attained molecular-level resolution under the severe instrumental limitations of his era; this empiricist methodology shaped the epistemology of modern molecular biology.